Adrenal cortex autoantibodies in subjects with normal adrenal function

The recent advances in our understanding of immunology have greatly improved our knowledge about the natural history of autoimmune diseases and, in particular, of autoimmune Addison's disease (Autoimmune AD). Autoimmune AD is a chronic disorder with a long preclinical period marked by the presence of adrenal cortex autoantibodies (ACAs). In this chapter the main data on this will be analyzed. The populations with the highest risk of Autoimmune AD are first relatives of patients with AAD and patients with autoimmune diseases, particularly those with chronic hypoparathyroidism or with premature ovarian failure. The best markers to identify the subjects at risk are ACAs detected by the immunofluorescence test on human or animal tissues, or 21-hydroxylase autoantibodies (21-OHAbs) detected by radioimmunoassay (RIA). The evaluation of adrenal cortex function in these individuals includes the basal determination of adrenocorticotropic hormone (ACTH), cortisol, aldosterone, plasma renin activity and cortisol after intravenous stimulation with synthetic ACTH. The multivariate analysis of the main factors (genetics, age, gender, titers of antibodies, pre-existing disease, status of the adrenal function) revealed that the risk of future AAD depends only on the presence of high antibody titers, chronic hypoparathyroidism or chronic candidiasis and adrenal dysfunction. On the basis of these parameters the risk of future Autoimmune AD can be calculated with an equation model. Patients with different risk scores need to be monitored at different time intervals, and those at high risk need to be strictly monitored and are the ideal subjects for future prevention trials.     

Survival of patients with bronchiectasis after the first ICU stay for respiratory failure

STUDY OBJECTIVES: Respiratory failure (RF) is a frequent cause of death among patients with bilateral bronchiectasis. An ICU admission is commonly required, and neither short-term or long-term outcomes have been studied. DESIGN: We performed a retrospective study over a 10-year period (January 1990 to March 2000). All patients with bilateral bronchiectasis admitted for the first time in the medical ICU for RF were reviewed. Patients with cystic fibrosis were excluded. MEASUREMENTS AND RESULTS: Forty-eight patients (mean age +/- SD, 63 +/- 11 years; mean simplified acute physiology score [SAPS] II, 32 +/- 12) of whom 25% received long-term oxygen therapy (LTOT) were identified. All the patients were treated with intensive medical care, associated with noninvasive ventilation in 13 patients (27%), and 26 patients (54%) required intubation. Nine patients (19%) died in the ICU. The 1-year mortality rate was 40%. Among the variables recorded at ICU admission, age > 65 years (p = 0.002), SAPS II score > 32 (p = 0.012), use of LTOT (p = 0.047), and intubation (p = 0.027) were associated with reduced survival in univariate analysis by Cox regression. Multivariate analysis by Cox proportional hazard model showed that age > 65 years (relative risk [RR], 2.70; 95% confidence interval [CI], 1.15 to 6.29) and use of LTOT (RR, 2.52; 95% CI, 1.15 to 5.54) were independently associated with reduced survival. CONCLUSIONS: We performed the first study providing information related to the impact of the first ICU stay for RF on long-term outcomes for patients with bilateral bronchiectasis. Age > 65 years and prior use of LTOT were associated with reduced survival.     

Successful prevention of multidrug resistant HIV mother-to-child transmission with enfuvirtide use in late pregnancy

The availability of antiretroviral therapy has dramatically reduced the risk of HIV mother-to-child transmission (MTCT). However, mothers infected with multidrug resistant HIV (MDR-HIV) are at increased risk of MTCT. We report the case of a pregnant patient infected with MDR-HIV in whom MTCT was avoided with enfuvirtide use in late pregnancy and elective caesarean section.     

Efficacy of a single intra-articular injection of ultra-high molecular weight hyaluronic acid for hip osteoarthritis: a randomized controlled study

Background

Viscosupplementation with hyaluronic acid (HA) is increasingly used for the treatment of hip osteoarthritis (OA). The purpose of this study was to compare the efficacy of intra-articular injections of an ultra-high molecular weight viscosupplement (UHMW-HA, Fermathron S) with a medium molecular weight hyaluronan (MMW-HA, Hyalubrix 60) in hip OA.

Methods

Fifty-four patients with hip OA grade 3 on the Kellgren/Lawrence scale were randomized. All infiltrations were performed under ultrasound guidance. Evaluation was performed preoperatively and at 1, 3, 6 and 12 months after infiltration. Patients were clinically evaluated using Lequesne index, VAS and WOMAC score.

Results

Fifty patients, including 27 in the MMW-HA group and 23 in the UHMW-HA group, completed the follow-up. No significant difference was found between the two groups in terms of VAS, WOMAC or Lequesne index preoperatively or at 1, 3, 6 and 12 months after viscosupplementation. A stratified analysis was performed to study the development over time of Lequesne index of patients aged ≤ 55 years, > 55 and, ≤ 70 years and > 70 years and Lequesne index was different between the three age-stratified subgroups only in the MMW-HA group. The subgroup of older patients showed a higher Lequesne index than the subgroups of younger patients (p < 0.05).

Conclusions

UHMW-HA is a safe and effective treatment for hip osteoarthritis. A single dose of UHMW-HA was as effective as two doses of MMW-HA resulting in similar reductions of pain and disability.

Study design

Multicenter, independent, prospective, randomized controlled trial with level of evidence 1.

     

Evaluation of a new line probe assay for rapid identification of gyrA mutations in Mycobacterium tuberculosis

Resistance of Mycobacterium tuberculosis to fluoroquinolones (FQ) results mostly from mutations in the gyrA gene. We developed a reverse hybridization-based line probe assay in which oligonucleotide probes carrying the wild-type gyrA sequence, a serine-to-threonine (S95T) polymorphism, and gyrA mutations (A90V, A90V-S95T, S91P, S91P-S95T, D94A, D94N, D94G-S95T, D94H-S95T) were immobilized on nitrocellulose strips and hybridized with digoxigenin-labeled PCR products obtained from M. tuberculosis strains. When a mutated PCR product was used, hybridization occurred to the corresponding mutated probe but not to the wild-type probe. A panel of M. tuberculosis complex strains including 19 ofloxacin-resistant (OFL-R) and 9 ofloxacin-susceptible (OFL-S) M. tuberculosis strains was studied for detection and identification of gyrA mutations by the line probe assay and nucleotide sequencing, in comparison with testing of in vitro susceptibility to FQ. Results were 100% concordant with those of nucleotide sequencing. The S95T polymorphism, which is not related to FQ resistance, was found in 5 OFL-S and 2 OFL-R strains; the other 17 OFL-R strains harbored single mutations associated with serine or threonine at codon 95. No mutations were found in the other OFL-S strains. Overall, on the basis of the MICs on solid medium, the new line probe assay correctly identified all OFL-S and 17 out of 19 (89.5%) OFL-R strains. A nested-PCR protocol was also evaluated for the assay to amplify PCR products from M. tuberculosis-spiked sputa, with a good specificity and a sensitivity of 2 x 10(3) M. tuberculosis CFU per ml of sputum.